Manufacture of preparations having an anti-emetic action



Patented June 193i UNITED STATES I PATEN OFFlCE 'MANUFACTURE OF PREPARATIONS HAVING AN ANTI- EMETIC ACTION of Germany No Drawing. Application March 8, 1934, Serial No. 714,584. In Ge rmany March 8, 1933 9 Claims (01. 167-68 The present invention concerns a manufacture of preparations having an anti-emetic action and it especially concerns the transformation of sparingly soluble compounds of rare earths into a colloidal state.

It is known, that the rare earths and. theircompounds havean anti-emetic action, that is to say they have the ability to reduce nausea. Thus for example cerium nitrate and other soluble cerium salts, also cerium oxalate, lanthanum oxalateand didymiumoxalate have been recommended as remedies against sickness during'pregnancy. The more sparingly soluble compounds are in this respect more active than the easily soluble compounds, in the. case of many of which the action is altogether absent. However, it has proved a disadvantage of the sparingly soluble compounds that their activity is somewhat unreliable; this may be attributed to the fact that they are resorbed in different degrees by any given person depending upon their nature and v upon the composition of the isaliva or of the con-- tents of the stomach.

- By the .present invention the eflicacy of the sparingly soluble compounds of the rare earths can be rendered appreciably more reliable by converting the compounds into the colloidal state. There are thus obtained preparations which read ily form a colloidal solution therefore they are easy to administer, and, especially when used in admixture with substances for improving the taste or for permitting the, preparation to be V shaped, for instance as a pill or tablet, they constitute advantageous remedies for the prevention of vomiting in sea-sickness, during pregnancy and so on.

The colloidal preparations can be made in various ways. The sparingly soluble compounds, especially thev sparingly soluble oxalates of the rare earths, such as cerium, didymium and lanthanum oxalates, canbe brought'into colloidal solution in a particularly advantageous manner with the aid of salts of organic polybasic oxyacids. Such acids are for example citric acid, malic acid and tartaric acid. The operation is facilitated in large degree by working in an alkaline medium, but an alkaline reaction of the solution is less'necessary the higher the'basicity of the oxy-acid. The process of peptization and the transformation into colloidal suspension proceed quite satisfactorily even in a neutral solution when conducted in the presence of sodium citrate. The proportion of the salt of the organic oxy-acid may vary within wide limits. Even relatively small proportions of a salt of an organic oxy-acid are sufllcient .to peptize the sparingly soluble salts of the rare earths as may be seen from the explanation .which follows hereinafter, e. g; Examples 1 to 6. The formation of the colloids is promoted by grinding the mixture in a ball-mill. By grinding alone, without addition of a salt of a polybasic organic oxy-acid it is however not possible to obtain a colloidal solution of, for instance, the oxalates, as will be evident from Examples 1 and 2 hereinafter.

If a-larger proportion of a salt of a polybasi'c oxy-acid is used, which approaches or exceeds a molecular proportion, their completely clear colloidal solutions of the sparingly soluble rare earth compounds are obtained.

4 The solutionsobtainable in accordance with the invention can be heated and concentrated without destroying their colloidal character; in

' fact the colloidal character persists even in the products obtained by drying the solutions. It is of especial advantage for the use of the preparations that peptization can be brought about even without the addition of a protective colloid. It is 7 however possible to use protective colloids together with the salts. of polybasic ,oxy-acids,

(compare Examples 3 and 4 hereinafter).

The sparingly-soluble compounds of the rare earths can also be converted into colloidal form with the aid of the usual protective colloids, such as gum arabic, degradation products of albumin and so on. In' this case it is advantageous to precipitate the sparingly soluble compound from an easily soluble salt in the presence of the protective colloid. Since however the compounds of the rare earths are converted into the colloidal state only with dimcult%, mere precipitation of the compoundin presen e of the protective colloid does not generally suflicer if however, the moist precipitated product still containing protective colloid is subjected to a grinding process,

there is obtained a colloidal solution which can either be used as such or can be converted by evaporation into a solid, dry preparation which can be redissolved to a. colloidal solution. It isv to be recommended in these cases that a further quantity of protective colloid should be added to the precipitated product before the grinding operation. The following examples illustrate the invention, the parts being, by weight: a t

' Example 1 5 parts of freshly precipitated oxalates. of

' a colloidal solution.

Example 2 I 5 parts of freshly precipitated oxalates of cerium earth metals are ground for 48 hours as in Example 1 together with 1 part. of water and 0.12 part of caustic soda solution of 20 per cent strength, but without a peptizer. No peptization occurs. If there is subsequently added 0.06 part of sodium citrate, the oxalates shortly become peptized and form a colloidal solution.

Example 3 1 part of freshly precipitated oxalates of cerium earth metals is ground together with 0.05 part of sodium citrate, 0.1 part of caustic soda solution of 20 per cent strength, 1 part of gum arabic' and 1.5 parts of water. A colloidal solution is obtained.

Example 4 1 part of freshly precipitated oxalates of cerium earth metals is ground together with 0.05 part of sodium tartrate, 0.1 part of caustic soda solution of 20 per cent strength, 1 part of gum arabic and 1.5 parts of water. A colloidal solution is obtained.

Example 5 4 parts of freshly precipitated cerium oxalateare ground for 48 hours together with 1 part of water, 0.06 part of sodium citrate and 0.12 part of caustic soda solution of 20 per cent strength. A colloidal solution is obtained.

Example 6 5 parts of freshly precipitated thorium oxalate are ground for 48 hours together with 1 part of water, 0.07 part of sodium citrate and-0.15 part of caustic soda solution of 20 per cent strength. The thorium oxalate passes'into the form of a colloidal solution.

Example 7 '1 part of the oxalates of cerium earth metals is heated whilst stirring together with 2 parts of sodium tartrate, 10 parts of water and 6 parts of caustic soda solution of 10 per cent strength. A colloidal suspension is formed.

Example 8 1 part of pure cerium oxalate, 4 parts of sodium malate, 15 parts of water and 3 parts of caustic soda solution of 10 per cent strength are heated to boiling, whereupon the insoluble residue gradually disappears.

Example 9 1 part of pure didymium oxalate, 2 parts of sodium tartrate, 10 parts of. water and 3 parts or caustic soda solution of 10 per cent strength are heated to boiling whilst stirring. The oxalate gradually-passes into the water.

parts of water.

Example 10 1 part of pure lanthanum oxalate, 2 parts of sodium tartrate, 10 parts of water and 3 parts of caustic soda solution of 10 per cent strength are'heated to boiling whilst stirring, whereupon the insoluble residue of the oxalate gradually disappears.

Example 11 To a solution of 10 parts of the nitrates o1 cerium earth metals in 1000 parts of distilled water there is added a solution of 15 parts of oxalic acid and 3 parts of gum arabic in The precipitate which is produced is allowed to settle, washed two or three times with water and-then ground in a ballmill whilst still wet with the addition of 2 parts.

of gum arabic. After some timethere is obtained a colloidal solution of cerium oxalate from which there can be obtained by evaporation a solid, dry preparation which can be redissolved to a colloidal solution. Instead of gum arabic there may be used another protective colloid, for

example an oxidation or degradation product of an albumin.

7 Example 12 "To a solution of 10 parts of cerium nitrate in 1000 parts of distilled water there is added a solution of 21 parts of sodium phosphate and 7 parts of gum arabic in 100 parts of water. The precipitate which is produced is washed and ground whilst still wet. After prolonged grinding there is obtained a colloidal solution of cerium phosphate.

What we claim is:

1. Preparing a colloid of a sparingly soluble salt of cerium, comprising treating said salt with an alkaline solution of a salt of an aliphatic polybasic oxy-aci d.

2. Preparing a colloid of a sparingly soluble salt of a metal taken from the group thorium, cerium, didymium and lanthanum, comprising treating said salt with an alkaline solution of a salt of an aliphatic polybasic oxy-acid.

3. As an anti-emetic, a colloidal, sparingly soluble salt of a metal taken from the group cerium, thorium, didymium and lanthanum.

4. As an anti-emetic, colloidal cerium oxalate.

5. An anti-emetic, comprising colloidal cerium oxalate as the principal ingredient, and an admixture of a. protective colloid.

6. An anti-emetic, comprising colloidal cerium oxalate as the principal ingredient, and an admixture of a salt of an aliphatic polybasic oxyacid.

7. An anti-emetic, comprising colloidal cerium oxalate as the principal'ingredient, and an ad- 1 mixture of a. salt of an aliphatic polybasic oxyacid, and of alkali.

8. A preparation having an anti-emetic action which contains cerium oxalate in the.colloidal state with the addition or gum arabic.

9. A preparation having an anti-emetic action which contains cerium oxalate in the colloidal state with the addition of an oxidation or degradation product of albumin.

CARL HERMANN, VON HOESSLE. RICHARD MULLER. 

